Comprehensive multi-omics analysis and experimental verification reveal PFDN5 is a novel prognostic and therapeutic biomarker for gastric cancer.

Prefoldin Subunit 5 (PFDN5) plays a critical role as a member of the prefoldins (PFDNs) in maintaining a finely tuned equilibrium between protein production and degradation. However, there has been no comprehensive analysis specifically focused on PFDN5 thus far. Here, a comprehensive multi-omics (transcriptomics, genomics, and proteomics) analysis, systematic molecular biology experiments (in vitro and in vivo), transcriptome sequencing and PCR Array were performed for identifying the value of PFDN5 in pan-cancer, especially in Gastric Cancer (GC). We found PFDN5 had the potential to serve as a prognostic and therapeutic biomarker in GC. And PFDN5 could promote the proliferation of GC cells, primarily by affecting the cell cycle, cell death and immune process etc. These findings provide novel insights into the molecular mechanisms and precise treatments of in GC.

Evaluation and Prediction Analysis of 3- and 5-Year Relative Survival Rates of Patients with Cervical Cancer: A Model-Based Period Analysis.

BACKGROUND: Cervical cancer remains a threat to female health due to high mortality. Clarification of the long-term trend of survival rate over time and the associated risk factors would be greatly informative to improve the prognosis of cervical cancer patients. METHODS: This retrospective study was based on data extracted from the Surveillance, Epidemiology, and End Results (SEER) database of the United States. The 3-year and 5-year overall survival rates of patients with cervical cancer during 2002-2006, 2007-2011, and 2012-2016 were analyzed. Period analysis was used to assess the variation in survival rate stratified by age, race, and socioeconomic status during the 15-year study period and then predicted the relative survival rate in the following period from 2017 to 2021. RESULTS: During 2002-2016, the 3-year relative survival rate of cervical cancer patients increased from 73.1% to 73.5% with a high jump between 2007 and 2011. This upward trend is expected to continue to 74.3% between 2017 and 2021. Patients older than 60 years, black ethnicity, or medium and high poverty status were likely to have a lower relative survival rate. CONCLUSION: This study confirmed the increased relative survival rate of cervical cancer patients over years and identified relevant risk factors. Targeted initiatives for elderly and socially underprivileged individuals may be able to mitigate inequality.

Why was the study conducted? Cervical cancer is one of the most common cancers endangering global women's health. Although there are currently relevant screening methods and vaccines, cervical cancer still leads to a higher risk of death in infected women and poses a serious threat to women's health. Therefore, it would be informative for future policy making if the risk factors affecting prognosis were assessed and the trend of long-term survival rate of patients with cervical cancer over time was predicted.What did the researchers do? We extracted data on cervical cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2002 and 2016 and used a model-based period analysis to assess the characteristics of the 3- and 5-year relative survival rates of cervical cancer patients stratified by age, race, and socioeconomic status. The relative survival rate for the period from 2017 to 2021 was projected.What did the researchers find? Our study found that the 3-year relative survival rate for cervical cancer patients increased from 73.1% to 73.5% between 2002 and 2016, with a jump between 2007 and 2011. Patients older than 60 years, those of black ethnicity, or those with medium and high poverty status were more likely to have a low relative survival rate.What do the findings mean? Our study confirms that the relative survival rate of cervical cancer patients has increased in recent years and has maintained an overall upward trend. Our findings suggest that age, race, and socioeconomic status are relevant risk factors. These findings would help us to predict future trends, better allocate medical resources, and optimize health policies to improve the prognosis of cervical cancer, such as targeting the elderly and other vulnerable groups.

Effect of spectrum broadening on photon-counting fiber Bragg grating sensing.

In a photon-counting fiber Bragg grating (FBG) sensing system, a shorter probe pulse width reaches a higher spatial resolution, which inevitably causes a spectrum broadening according to the Fourier transform theory, thus affecting the sensitivity of the sensing system. In this work, we investigate the effect of spectrum broadening on a photon-counting FBG sensing system with a dual-wavelength differential detection method. A theoretical model is developed, and a proof-of-principle experimental demonstration is realized. Our results give a numerical relationship between the sensitivity and spatial resolution at the different spectral widths of FBG. In our experiment, for a commercial FBG with a spectral width of 0.6 nm, an optimal spatial resolution of 3 mm and a corresponding sensitivity of 2.03 nm-1 can be achieved.

Ultra-narrow linewidth and a low-noise cascading Brillouin random fiber laser with a dual pump.

A cascading Brillouin random fiber laser with a dual pump (DP-CBRFL) is proposed and demonstrated. The DP-CBRFL can improve the Brillouin gain significantly to achieve an ultra-narrow linewidth (95.5 Hz) with 200 mW pump power, due to two cascading Brillouin gain fibers with an identical Brillouin frequency shift. Compared with the general Brillouin random fiber laser, the proposed random fiber laser has a more stable Brillouin gain spectrum and a lower mode density, which makes it have a lower intensity noise and frequency noise, especially in the low-frequency range. Meanwhile, it exhibits a high slope efficiency of 28% even if the pump power has reached 1.1 W due to the strong suppression ability of the high-order Stokes light.

Polyamine metabolism patterns characterized tumor microenvironment, prognosis, and response to immunotherapy in colorectal cancer.

BACKGROUND: Changes in Polyamine metabolism (PAM) have been shown to establish a suppressive tumor microenvironment (TME) and substantially influence the progression of cancer in the recent studies. However, newly emerging data have still been unable to fully illuminate the specific effects of PAM in human cancers. Here, we analyzed the expression profiles and clinical relevance of PAM genes in colorectal cancer (CRC). METHODS: Based on unsupervised consensus clustering and principal component analysis (PCA) algorithm, we designed a scoring model to evaluate the prognosis of CRC patients and characterize the TME immune profiles, with related independent immunohistochemical validation cohort. Through comparative profiling of cell communities defined by single cell sequencing data, we identified the distinct characteristics of polyamine metabolism in the TME of CRC. RESULTS: Three PAM patterns with distinct prognosis and TME features were recognized from 1224 CRC samples. Moreover, CRC patients could be divided into high- and low-PAMscore subgroups by PCA-based scoring system. High PAMscore subgroup were associated to more advanced stage, higher infiltration level of immunosuppressive cells, and unfavorable prognosis. These results were also validated in CRC samples from other public CRC datasets and our own cohort, which suggested PAM genes were ideal biomarkers for predicting CRC prognosis. Notably, PAMscore also corelated with microsatellite instability-high (MSI-H) status, higher tumor mutational burden (TMB), and increased immune checkpoint gene expression, implying a potential role of PAM genes in regulating response to immunotherapy. To further confirm above results, we demonstrated a high-resolution landscape of TME and cell-cell communication network in different PAM patterns using single cell sequencing data and found that polyamine metabolism affected the communication between cancer cells and several immune cells such as T cells, B cells and myeloid cells. CONCLUSION: In total, our findings highlighted the significance of polyamine metabolism in shaping the TME and predicting the prognosis of CRC patients, providing novel strategies for immunotherapy and the targeting polyamine metabolites.

Exploring the role of pyroptosis in shaping the tumor microenvironment of colorectal cancer by bulk and single-cell RNA sequencing.

BACKGROUND: Emerging studies have shown that pyroptosis plays a non-negligible role in the development and treatment of tumors. However, the mechanism of pyroptosis in colorectal cancer (CRC) remains still unclear. Therefore, this study investigated the role of pyroptosis in CRC. METHODS: A pyroptosis-related risk model was developed using univariate Cox regression and LASSO Cox regression analyses. Based on this model, pyroptosis-related risk scores (PRS) of CRC samples with OS time > 0 from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database were calculated. The abundance of immune cells in CRC tumor microenvironment (TME) was predicted by single-sample gene-set enrichment analysis (ssGSEA). Then, the responses to chemotherapy and immunotherapy were predicted by pRRophetic algorithm, the tumor immune dysfunction and exclusion (TIDE) and SubMap algorithms, respectively. Moreover, the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing dataset (PRISM) were used to explore novel drug treatment strategies of CRC. Finally, we investigated pyroptosis-related genes in the level of single-cell and validated the expression levels of these genes between normal and CRC cell lines by RT-qPCR. RESULTS: Survival analysis showed that CRC samples with low PRS had better overall survival (OS) and progression-free survival (PFS). CRC samples with low PRS had higher immune-related gene expression and immune cell infiltration than those with high PRS. Besides, CRC samples with low PRS were more likely to benefit from 5-fluorouracil based chemotherapy and anti-PD-1 immunotherapy. In novel drug prediction, some compounds such as C6-ceramide and noretynodrel, were inferred as potential drugs for CRC with different PRS. Single-cell analysis revealed pyroptosis-related genes were highly expressed in tumor cells. RT-qPCR also demonstrated different expression levels of these genes between normal and CRC cell lines. CONCLUSIONS: Taken together, this study provides a comprehensive investigation of the role of pyroptosis in CRC at the bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) levels, advances our understanding of CRC characteristics, and guides more effective treatment regimens.

Berberine protects cyclophosphamide and busulfan-induced premature ovarian insufficiency in mouse model.

Premature ovarian insufficiency (POI) is a clinical syndrome that declines ovarian function in women. Berberine (BBR) is a compound with anti-inflammatory, antioxidant, and anti-apoptotic activities. However, the role of BBR on POI is still unknown. In this study, we investigated the role of BBR on ovarian function decline by establishing a POI mouse model using cyclophosphamide (CTX) and busulfan (BU). Our results showed that POI was attenuated by BBR, which was evidenced by enhanced body weight and ovarian weight, improved morphology of ovary, increased the number of healthy follicles, decreased the production of atretic follicles and restored serum hormone levels, including estradiol, anti-Müllerian hormone and follicle-stimulating hormone. In addition, we showed that germ cell function markers, mouse vasa homologue (MVH) and octamer-binding transcription factor 4 (OCT4) were enhanced by BBR, at both protein and mRNA levels. Furthermore, our results revealed that BBR inhibited inflammation and oxidative stress by reducing nuclear factor kappa B (NF-κB) and enhancing nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. Taken together, we demonstrate that BBR can effectively improve ovarian function in POI mice, which is mainly mediated by reducing oxidative stress and inflammatory response. Our study also provides new strategy for POI treatment.

Roxadustat alleviates nitroglycerin-induced migraine in mice by regulating HIF-1α/NF-κB/inflammation pathway.

Sensitization of central pain and inflammatory pathways play essential roles in migraine, a primary neurobiological headache disorder. Since hypoxia-inducible factor-1α (HIF-1α) is implicated in neuroprotection and inflammation inhibition, herein we investigated the role of HIF-1α in migraine. A chronic migraine model was established in mice by repeated injection of nitroglycerin (10 mg/kg, i.p.) every other day for 5 total injections. In the prevention and acute experiments, roxadustat, a HIF-1α stabilizer, was orally administered starting before or after nitroglycerin injection, respectively. Pressure application measurement, and tail flick and light-aversive behaviour tests were performed to determine the pressure pain threshold, thermal nociceptive sensitivity and migraine-related light sensitivity. At the end of experiments, mouse serum samples and brain tissues were collected for analyses. We showed that roxadustat administration significantly attenuated nitroglycerin-induced basal hypersensitivity and acute hyperalgesia by improving central sensitization. Roxadustat administration also decreased inflammatory cytokine levels in serum and trigeminal nucleus caudalis (TNC) through NF-κB pathway. Consistent with the in vivo results showing that roxadustat inhibited microglia activation, roxadustat (2, 10, and 20 µM) dose-dependently reduced ROS generation and inflammation in LPS-stimulated BV-2 cells, a mouse microglia cell line, by inhibiting HIF-1α/NF-κB pathway. Taken together, this study demonstrates that roxadustat administration ameliorates migraine-like behaviours and inhibits central pain sensitization in nitroglycerin-injected mice, which is mainly mediated by HIF-1α/NF-κB/inflammation pathway, suggesting the potential of HIF-1α activators as therapeutics for migraine.

A case report and literature review on nephrogenic alveolar soft part sarcoma: clinicopathological manifestations and genetic features.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare kind of malignant soft tissue tumor with undefined differentiation, of which the incidence rate accounts for only 0.5-1.0% among all kinds of soft tissue tumors. An even rarer ASPS occurs in kidney. CASE PRESENTATION: Here we reported a case of a 7-year-old girl diagnosed with nephrogenic ASPS, regarding the analyses of the incidence, clinical manifestation, pathology and genetic diagnosis, in order to deepen the recognition of the disease. CONCLUSIONS: ASPS is very rare, and tends to occur to young patients. It is very significant to precisely diagnose ASPS at an early stage, which will be the key point for the following treatment choices and prognosis.

Clinical experience of bench surgery combined with autotransplantation after three-dimensional laparoscopic nephrectomy for the treatment of highly complex renal tumor.

OBJECTIVE: To assess the feasibility and safety of three-dimensional (3D) laparoscopic nephrectomy in combination with bench surgery and autotransplantation for treating highly complex renal tumors. MATERIALS AND METHODS: The clinical data of six patients with highly complex renal cell carcinoma were collected. All patients underwent 3D laparoscopic nephrectomy in combination with bench surgery and autotransplantation by the same surgeons, two of them had previously undergone laparoscopic partial nephrectomy for contralateral renal cancer. RESULTS: The total operative time was 366 ± 65 min, the warm ischemia time (WIT) was 1.3 ± 0.4 min, and the cold ischemia time was 121 ± 26 min. While one patient received a diluted autologous blood transfusion, the intraoperative blood loss was 217 ± 194 ml. No increase in the serum creatinine (SCr) level was observed at postoperative day 30 compared with the preoperative time, and none of the patients received dialysis either during the hospital stay or to date. Although one patient underwent nephrectomy due to tumor recurrence in the transplanted kidney, the others reported no tumor recurrence or distant metastases on imaging to date. CONCLUSION: 3D laparoscopic nephrectomy, when combined with bench surgery and autotransplantation, can become a feasible option for treating highly complex renal cell carcinoma cases when expecting to preserve renal function maximally.

A Resource-Adaptive Routing Scheme with Wavelength Conflicts in Quantum Key Distribution Optical Networks.

Quantum key distribution (QKD) has great potential in ensuring data security. Deploying QKD-related devices in existing optical fiber networks is a cost-effective way to practically implement QKD. However, QKD optical networks (QKDON) have a low quantum key generation rate and limited wavelength channels for data transmission. The simultaneous arrival of multiple QKD services may also lead to wavelength conflicts in QKDON. Therefore, we propose a resource-adaptive routing scheme (RAWC) with wavelength conflicts to achieve load balancing and efficient utilization of network resources. Focusing on the impact of link load and resource competition, this scheme dynamically adjusts the link weights and introduces the wavelength conflict degree. Simulation results indicate that the RAWC algorithm is an effective approach to solving the wavelength conflict problem. Compared with the benchmark algorithms, the RAWC algorithm can improve service request success rate (SR) by up to 30%.

Association of tumor mutational burden with genomic alterations in Chinese urothelial carcinoma.

The tumor mutational burden (TMB) calculated by whole-exome sequencing (WES) is a promising biomarker for the response to immune checkpoint inhibition (ICIs) in solid tumors. However, WES is not feasible in the routine clinical setting. In addition, the characteristics of the TMB in Chinese urothelial carcinoma (UC) are unclear. The aim of this study was to demonstrate the reliability of an Acornmed 808 panel and analyze the characteristics of the TMB in Chinese UC. An Acornmed 808 panel was designed and virtually validated using UC data from the cancer genome atlas (TCGA). Comprehensive analysis of sequencing and clinical data was performed to explore the characteristics of the TMB for 143 Chinese UC patients. Compared to the TMB calculated with random 808-, 500-, and 250-gene panels, the TMB calculated with the Acornmed 808 panel was closer to that calculated by WES. There were marked disparities in the mutational landscape and TMB between Chinese and TCGA UC data. The TMB was negatively associated with copy number variation (CNV). In contrast, the TMB was positive correlation with numbers of mutated DDR genes. Exposure to aristolochic acid signature was observed only in the TMB-high groups. The Acornmed 808 panel is a clinically practical method to assess the TMB. The TMB was associated with the DDR gene status and CNV counts and might be a biomarker for further stratification of UC patients. The study suggested that patients with high TMB may have a unique carcinogenic mechanism.

Electric Field-Controlled Damping Switches of Coupled Dirac Plasmons.

For quasiparticle systems, the control of the quasiparticle lifetime is an important goal, determining whether the related fascinating physics can be revealed in fundamental research and utilized in practical applications. Here, we use double-layer graphene with a boron nitride spacer as a model system to demonstrate that the lifetime of coupled Dirac plasmons can be remotely tuned by electric field-controlled damping pathways. Essentially, one of the graphene layers serves as an external damping amplifier whose efficiency can be controlled by the corresponding doping level. Through this damping switch, the damping rate of the plasmon can be actively tuned up to 1.7 fold. This Letter provides a prototype design to actively control the lifetime of graphene plasmons and also broadens our horizon for the damping control of other quasiparticle systems.

Height and pelvic lesion number: Do they have a positive relationship with postoperative recurrence in adolescent endometriosis?-A retrospective clinical analysis of 89 adolescent endometriosis in China.

BACKGROUND: Adolescent endometriosis is a special type of endometriosis. Its diagnosis is often delayed. This study aimed to share the treatment experience of adolescent endometriosis and analyze the clinical manifestation, clinical stage, and risk factors of postoperative recurrence in China. METHODS: Eighty-nine cases of adolescent endometriosis over 7 years in a single institution were reviewed. Demographic, clinical outcome measures were collected. RESULT: The cumulative incidence rates of postoperative recurrence at years 1, 2, 3, 4, and 5 were 13.2%, 15.09%, 16.98%, 20.75%, and 20.75%, respectively. The risk factors associated with postoperative recurrence were disease stage, number of lesions, and height. In multivariate analysis, the independent risk factors of postoperative recurrence were height (RR: 1.132, 95% CI: 1.018-1.260) and the number of pelvic lesions (three or more, RR: 4.202, 95% CI: 1.013-17.433). CONCLUSION: Taller patients and those who had multiple lesion sites (≥3) should receive more attention, because they have a higher possibility of relapse after surgery than their counterparts. This finding can guide the postoperative treatment of adolescent patients with endometrioma.

Spontaneous Folding Growth of Graphene on h-BN.

Graphene has been the subject of much research, with structural engineering frequently used to harness its various properties. In particular, the concepts of graphene origami and kirigami have inspired the design of quasi-three-dimensional graphene structures, which possess intriguing mechanical, electronic, and optical properties. However, accurate controlling the folding process remains a big challenge. Here, we report the discovery of spontaneous folding growth of graphene on the h-BN substrate via adopting a simple chemical vapor deposition method. Folded edges are formed when two stacked graphene layers share a joint edge at a growth temperature up to 1300 °C. Using first-principles density functional theory calculations, the bilayer graphene with folded edges is demonstrated to be more stable than that with open edges. Utilizing this novel growth mode, hexagram bilayer graphene containing entirely sealed edges is eventually realized. Our findings provide a route for designing graphene devices with a new folding dimension.

An Effective Approach to Improve the Thermal Conductivity, Strength, and Stress Relaxation of Carbon Nanotubes/Epoxy Composites Based on Vitrimer Chemistry.

An effective method was developed to improve the interfacial interaction between Mutiwalled carbon nanotubes (MWCNTs) and epoxy matrix. The performance of thermal conductivity and strength of the epoxy vitrimer were enhanced by polydopamine (PDA) coating. Polydopamine is a commonly used photothermal agent, which of course, was effective in modifying MWCNTs used in photoresponsive epoxy resin. The surface temperature of the epoxy composite with 3% MWCNTs@PDA fillers added increased from room temperature to 215 °C in 48 s. The metal-catechol coordination interactions formed between the catechol groups of PDA and Zn2+ accelerated the stress relaxation of epoxy vitrimer. Moreover, the shape memory, repairing, and recycling of epoxy vitrimer were investigated. Therefore, dopamine coating is a multifunctional approach to enhance the performance of epoxy vitrimer.

Down-Regulation of Lipid Metabolism in the Hepatopancreas of Shrimp Litopenaeus vannamei upon Light and Heavy Infection of Enterocytozoon hepatopenaei: A Comparative Proteomic Study.

Enterocytozoon hepatopenaei (EHP) is the pathogen of hepatopancreatic microsporidiosis (HPM) in shrimp. The diseased shrimp Litopenaeus vannamei exhibits a slow growth syndrome, which causes severe economic losses. Herein, 4D label-free quantitative proteomics was employed to analyze the hepatopancreas of L. vannamei with a light (EHPptp2 < 103 copies/50 ng hpDNA, L group) and heavy (EHPptp2 > 104 copies/50 ng hpDNA, H group) load of EHP to better understand the pathogenesis of HPM. Exactly 786 (L group) and 1056 (H group) differentially expressed proteins (DEPs) versus the EHP-free (C group) control were mainly clustered to lipid metabolism, amino acid metabolism, and energy production processing. Compared with the L group, the H group exhibited down-regulation significantly in lipid metabolism, especially in the elongation and degradation of fatty acid, biosynthesis of unsaturated fatty acid, metabolism of α-linolenic acid, sphingolipid, and glycerolipid, as well as juvenile hormone (JH) degradation. Expression pattern analysis showed that the degree of infection was positively correlated with metabolic change. About 479 EHP proteins were detected in infected shrimps, including 95 predicted transporters. These findings suggest that EHP infection induced the consumption of storage lipids and the entire down-regulation of lipid metabolism and the coupling energy production, in addition to the hormone metabolism disorder. These were ultimately responsible for the stunted growth.

Rate-Compatible LDPC Codes for Continuous-Variable Quantum Key Distribution in Wide Range of SNRs Regime.

Long block length rate-compatible low-density parity-compatible (LDPC) codes are designed to solve the problems of great variation of quantum channel noise and extremely low signal-to-noise ratio in continuous-variable quantum key distribution (CV-QKD). The existing rate-compatible methods for CV-QKD inevitably cost abundant hardware resources and waste secret key resources. In this paper, we propose a design rule of rate-compatible LDPC codes that can cover all potential SNRs with single check matrix. Based on this long block length LDPC code, we achieve high efficiency continuous-variable quantum key distribution information reconciliation with a reconciliation efficiency of 91.80% and we have higher hardware processing efficiency and lower frame error rate than other schemes. Our proposed LDPC code can obtain a high practical secret key rate and a long transmission distance in an extremely unstable channel.

Frictional Drag Effect between Massless and Massive Fermions in Single-Layer/Bilayer Graphene Heterostructures.

The emergence of two-dimensional layered materials offers an excellent opportunity for the fabrication of double-layer electron systems that are in close proximity but electronically isolated. In this work, heterostructures consisting of one single-layer graphene (SLG) and one bilayer graphene (BLG) separated by an ultrathin hBN layer are successfully fabricated, enabling the experimental investigation of the interlayer frictional drag effect between massless and massive fermions. With varying carrier densities, a giant positive peak of drag response emerges at the double neutrality point, around which nonmonotonic temperature dependent behaviors of drag resistance are further observed. These observations can be attributed to the anticorrelations in the distributions of e-h puddles between layers. More importantly, as the system shifts toward the strong coupling regime, the carrier density dependence of drag resistance Rdrag shows a crossover from 1/n3 to 1/n2 for the density matched cases, which is a unique characteristic predicted for massless-massive fermion systems. Consequently, a generalized carrier dependent expression (1/(|nS| + |nB|)2) is obtained for the strong coupling regime, where nS and nB are the carrier densities of SLG and BLG, respectively. Our study provides insight into the electronic frictional effects between massless and massive fermions and thus will promote the investigations of interlayer interactions in hybrid structures hosting different types of carriers.

A New Strategy to Synthesize α,ω-Dihydroxy Multiblock Copolymers via [CpRu(CH3 CN)3 ]PF6 /Quinaldic Acid Catalyst.

In this study, a new strategy to synthesize random and alternating multiblock copolymers (MBCs) by the polycondensation of macromonomers' terminal hydroxyl groups with [CpRu(CH3 CN)3 ]PF6 /quinaldic acid as the catalyst is reported, which is often used for the preparation of a variety of biological small molecules via the reaction of allyl ethers. The degrees of hydroxyl functionality (Fn ) of the MBCs are assessed by titration, and the presence of hydroxyl on both the ends of MBCs is also confirmed by a chain-extension experiment of the ring-opening polymerization of D,L-lactide.